Journal of Sleep Research

ABSTRACT Purpose: Survivors of severe COVID-19 commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. Methods: We conducted a cross-sectional analysis of the RAFT COVID study, a national multicenter longitudinal cohort of severe prolonged COVID-19 survivors. We included participants who completed validated surveys at 1-year from hospitalization for depression (PHQ-9) and fatigue (FACIT-Fatigue). We described correlation of FACIT-fatigue with the PHQ9, and separately with PHQ-2 and PHQ-7, which both omit the two items we hypothesized are influenced by fatigue: tiredness and sleeping. Using a MIMIC model, we performed differential item functioning to evaluate the impact of fatigue on depression directly through these two questions and indirectly with the latent depression construct. We then compared PHQ-7 to PHQ-9 scores by fatigue status. Results: Among 82 participants, 61.0% reported fatigue (reverse-scored FACIT-Fatigue[&ge;]9), and 15.9% moderately severe depression (PHQ-9[&ge;]10). FACIT-fatigue was strongly correlated with PHQ-9 (r=.87, p<.001), but less so for PHQ-2 (r=.76, p<.001) and PHQ-7 (r=.82, p<.001). The MIMIC model identified significant direct effects on tiredness ({lambda}=.89, p<.001) and sleep ({lambda}=.52, p<.001). Among fatigued participants, the rescaled PHQ-7 was lower than the PHQ-9 (median of 4.5, IQR 1.50-9.75, vs 7, IQR 4-9.75). Conclusions: Fatigue significantly inflated depression symptoms in severe COVID-19 survivors through tiredness and sleeping PHQ-9 items. PHQ-2 may better screen for true depressive symptoms in PICS, minimizing the risk of misdiagnosis and overtreatment.

Motor memory retention is impaired in Parkinson's disease (PD), affecting long-term rehabilitation outcomes. It appears that NREM sleep could be beneficial for consolidation processes in PD, and could be leveraged with non-invasive sleep interventions. This study examined the effect of auditory targeted memory reactivation (TMR) during NREM sleep on the retention of a motor sequence learning finger tapping task in 20 PD and 20 healthy older adults (HOA). TMR was applied during a 2-hour nap and its effect on motor retention was post-nap, after 24-hours and with a dual-task. The impact of TMR on sleep electrophysiology was also evaluated. Results showed no effect of TMR on motor retention or dual-tasking, with no difference between the groups. However, the TMR intervention did increase slow-wave density and decreased spindle density in both groups, and slow-wave amplitude during the presentation of the auditory cues was positively associated with performance in HOA. In conclusion, TMR applied during a 2 hour nap did not enhance motor retention, but the changes in sleep physiological features could be linked to a possible underlying effect on memory processing that warrants further investigation.

ABSTRACT Background Medical students face demanding academic schedules and elevated stress levels, predisposing them to poor sleep quality. Sleep hygiene, a set of behavioural and environmental practices aimed at optimising sleep, has been identified as a modifiable determinant of sleep quality, yet its role among medical students in Sudan remains unstudied. Objectives To assess current sleep hygiene practices among medical students at UMST and determine their association with sleep quality outcomes. Methods A facility based cross-sectional study was conducted at UMST among 240 medical students from three academic batches (3rd, 4th, and 5th year), selected via stratified random sampling. Data were collected using two validated self administered instruments: the Pittsburgh Sleep Quality Index (PSQI) and the Sleep Hygiene Index (SHI). Descriptive statistics, independent sample t tests, one way ANOVA, chi-square tests, Pearson correlation, and binary logistic regression were performed using SPSS version 23. Results Poor sleep quality (PSQI >5) was prevalent in 72.1% of participants (mean PSQI 7.25 +/- 2.66), and poor sleep hygiene (SHI >16) in 92.5% (mean SHI 27.1 +/- 7.9). SHI score (continuous) was the only significant independent predictor of sleep quality on logistic regression (OR = 1.13 per unit increase; 95% CI: 1.08-1.19; p < 0.001), equivalent to a 3.4-fold increase in odds per 10-unit rise in SHI score. Female sex was additionally identified as a significant predictor (OR = 1.88; 95% CI: 1.00-3.53; p = 0.049). A significant positive correlation was observed between PSQI and SHI scores (r = 0.359, p < 0.001). Conclusion Poor sleep hygiene is highly prevalent among UMST medical students and is the most significant modifiable predictor of poor sleep quality, with each unit increase in SHI score increasing the odds of poor sleep quality by 13%. These findings highlight a gap in sleep health education within Sudanese medical institutions and support the integration of targeted sleep hygiene interventions into the medical curriculum. Keywords: sleep hygiene; sleep quality; medical students; Sudan; PSQI; SHI; cross-sectional study

Background: Narcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectives: We aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. Methods: We analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. Results: Our findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. Conclusion: Taken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control.

We completed a video-based, four-night, in-home, level 3 sleep apnea study of healthy, low-risk pregnant participants and their bed partners in order to characterize sleep physiology in the third trimester of pregnancy. Demographic, anthropometric, and baseline sleep health characteristics were recorded, and the NightOwl home sleep apnea test device was used to measure sleep breathing, posture, and architecture parameters. Symptoms of restless legs syndrome were elicited in the exit interview. Forty-one pregnant participants and 36 bed partners completed the study. Bed partners had a significantly higher prevalence of sleep apnea than their pregnant co-sleepers (31% vs. 5.9%). Bed partners also had more severe sleep apnea than their pregnant co-sleepers, and this persisted on an adjusted analysis for baseline differences in factors known to increase risk of sleep apnea. In pregnant participants, increasing gestational age was found to be protective against mild respiratory events but not more severe events. While the correlation between STOP-Bang score and measures of sleep apnea severity was weak, an affirmative response to the witnessed apneas item on the STOP-Bang questionnaire was a strong predictor of more severe sleep apnea for all participants. Smoking history also increased sleep apnea risk. Pregnant participants had lower sleep efficiency and longer self-reported sleep onset latency. Restless legs syndrome was experienced by 39.5% of the pregnant participants but no bed partners. From a sleep breathing perspective, people with healthy, low-risk pregnancies have better sleep than their bed partners despite lower sleep efficiency and higher rates of restless legs syndrome.

Social prescribing has assumed increasing dominance in policy and practice internationally, including in the UK, where it has an increasing role in addressing social needs such as isolation, and social determinants of ill health. Although General Practitioners are perceived as key referral sources, social workers in one locality were found to play a significant role in referral. This suggests that the social work role in this context has been under recognised and under explored. This study sought to explore social workers' perceptions and experiences of social prescribing through an online survey conducted from January to June 2022. All UK social workers were eligible to participate, regardless of whether they had made referrals. A total of 105 responses were collected from all UK nations. Data was analysed using inductive thematic analysis. Four key themes were generated: contended and contested boundaries; complementary spaces; delineated spaces of simplicity and complexity; social work under threat. Participants recognised that social prescribing could provide valuable client support and could be a useful resource for social workers. However, they also expressed concerns about overlapping professional boundaries and the potential for social prescribing to encroach on social work, perceiving it as most appropriate for the delivery of support to those with 'low level' needs.

BackgroundScalable, low-burden behavioral interventions are needed to address rising subclinical mental health symptoms. However, few randomized controlled trials have evaluated ultra-brief, remotely delivered, meditation using multimodal outcome assessment under real-world conditions. MethodsWe conducted a fully remote randomized controlled trial (ClinicalTrials.gov: NCT06014281) evaluating a focused-attention meditation intervention delivered via brief instructor training and independent daily practice. A total of 299 meditation-naive adults were randomized to immediate intervention or waitlist control in a delayed-intervention design. Participants practiced [&ge;]10 minutes daily for 8 weeks within a 16-week study. Outcomes included validated self-report measures, web-based cognitive tasks, and wearable-derived physiological metrics. ResultsAcross randomized and within-participant replication phases, the intervention was associated with significant reductions in anxiety and mind wandering, with effects remaining stable during 8-week follow-up. Improvements were greatest among participants with higher baseline symptom burden. Sleep disturbance improved selectively among individuals with poorer baseline sleep. Secondary outcomes, including rumination, perceived stress, social connectedness, and quality of life, also improved. Cognitive performance showed modest improvements primarily among lower-performing participants. Resting heart rate exhibited nominal reductions. ConclusionsAn ultra-brief, fully remote meditation intervention requiring 10 minutes per day was associated with sustained improvements in psychological functioning and smaller, baseline-dependent effects on cognition in a non-clinical population. These findings support digital delivery of low-dose meditation as a scalable preventive mental health strategy.

Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

This analysis evaluates the feasibility and psychometric properties of daily digital cognitive assessments (DCAs) delivered on smartphones using data from the large, international Identifying Digital Endpoints to Assess FAtigue, Sleep and acTivities of daily living in Neurodegenerative disorders and Immune-mediated inflammatory diseases (IDEA-FAST) study. The data we analyse were collected from patients with neurodegenerative diseases (NDDs) and immune-mediated inflammatory diseases (IMIDs), and healthy controls (a subset who participated in all phases of the study, total N=977) in their own homes. These data were obtained alongside data from other devices that monitored physiology, kinematics, and sleep quality. Following a baseline visit, participants were remotely monitored via three scheduled daily sessions for 6-7 days in each of 4 active assessment phases (APs). APs were separated by 6-week intervals. Daily schedules comprised a morning psychomotor vigilance task (PVT) with eDiary, afternoon session (eDiary only), and an evening digit symbol substitution task (DSST) with eDiary. We evaluated session coverage using logistic mixed effects, test-retest reliability using ICCs, disease impacts on performance using linear mixed effect ANCOVA, and familiarisation using linear mixed effects. Overall coverage was 67.5% for the PVT and 77.0% for the DSST, with no significant differences between the healthy volunteers and disease cohorts. Coverage varied significantly by time-of-day (Evening > Morning > Afternoon), and improved with age, with an interaction revealing session time-of-day affected older participants less, all p < .001. Coverage was highest in AP 1 and reduced in subsequent APs. AP-day effects on coverage interacted significantly with AP, with a modest decline over AP 1, and the pattern reversed in APs 2-4. Baseline reliability was good (> .70) for both PVT mean reaction time and DSST total correct across all cohorts, and the movement-based measure from the DSST ranged [.55, .75], with lower values in the Parkinson's Disease and Primary Sjogren's Syndrome cohorts. Both tasks showed significant cohort effects, with performance in IMID cohorts intermediate between healthy controls and NDD. Longitudinal analysis revealed significant familiarisation effects in DSST. This was greatest in healthy controls, with significant attenuation of these effects in disease cohorts. No effect of familiarisation was seen in the PVT. Collectively, these results support the usefulness of at-home cognitive assessment on smartphones. Brief measures of cognition can be captured remotely in disease as well as controls with good adherence and sensitivity to distinguish known patient groups from healthy controls.

Background: The timing of energy intake could be important in the development of obesity. However, most observational evidence stems from adults, anthropometric defined obesity outcomes, single meal timing phenotyping, and traditional regression modeling. Objective: We aimed to describe meal timing patterns in adolescents and determine if they associated with fat mass by modeling the median and all other percentiles of the frequency distribution. Methods: We analyzed data from the Sleep and Growth Study 2 (S-Grow2, N=286, 12-13y). Participants completed 3-day 24-hour dietary recalls and time stamped eating occasions were used to define 8 meal timing traits, with aide from self-reported wake and bed timing. Principal component analysis (PCA) identified multi-dimensional meal timing patterns. Fat mass index (FMI) was estimated using dual energy X-ray absorptiometry. Quantile regression assessed if there were associations between meal timing traits and FMI across the entire FMI frequency distribution. Results: The typical first and last eating occasions were 8:00am (40 minutes after waking) and 8:00pm (2.7 hours before sleep), respectively, thus the eating period typically lasted 11.5 hours per day. The typical eating period midpoint was 2:15pm, and the timing when 50% of energy intake was consumed typically occurred at 3:15pm. PCA revealed three meal timing patterns: 1) Delayed Start, Condensed Eating Period (43% of variance; shorter eating period and delayed timing of first eating); 2) Late, Sleep Proximal Eating (30% of variance; later timing of last eating and extended eating period), and 3) Later Energy Intake (10% of variance; delayed energy intake midpoint). Higher scores for the Delayed Start, Condensed Eating Period pattern associated with higher body mass index and FMI at the upper tails of their distributions. Conclusions: Distinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity.

Background Individuals experiencing or at risk of homelessness face substantial barriers to preventive eye care that are poorly addressed by standard service models. Interdisciplinary optometry-social work collaboration offers a rights-based approach to improving engagement and continuity of care. Methods A convergent mixed-methods study was conducted between February and August 2024 at a multidisciplinary community centre. Clients experiencing or at risk of homelessness received integrated optometry and social work assessment and were prioritised as high, medium, or low based on combined clinical and social risk. Social work follow-up was guided by the Triple Mandate and W-Questions framework. Quantitative data were summarised using mean (SD), median [IQR], or n (%). Qualitative case notes were analysed using content analysis with inductive coding and secondary review for consistency. Results A total of 165 clients had priority categories coded (high: 68; medium: 47; low: 154). Demographic data were available for 132 clients (60% male; mean age 49.5 years [SD 16]); 27% had not completed high school, 89% reported weekly income below AUD 1000, and 28% had vision impairment. Two hundred forty-five case-note entries were consolidated into 146 unique records. SMS (46%) and phone calls (38%) were the most documented contact methods, although only 21% of calls were answered; missed calls (13%) and disconnected numbers (7%) were common. Multi-modal contact was more frequently documented for higher-priority clients. Appointment assistance was the most recorded facilitator (71%), while rights-based supports, including interpreter and transport assistance, were infrequently documented (<=5%). Qualitative analysis identified unstable communication, reliance on informal supports, and service fragmentation as key influences on recall outcomes. Conclusion This study supports an interdisciplinary, rights-based optometry-social work model to address barriers to preventive eye care among people experiencing or at risk of homelessness. Embedding structured handovers and tiered recall processes within community-based services may strengthen continuity and accountability for high-priority clients. Future implementation should evaluate outcomes related to equity of reach, service integration, and sustained engagement in care.

Chronotype reflects individual circadian preference for timing of sleep, wakefulness, and peak performance and has been linked to variability in prefrontal cognitive function across the day. Whether chronotype independently relates to dual-task gait cost (DTC) and whether this relationship differs by cognitive task domain is unclear. Sixty-nine healthy young adults (37 female; mean age 21.3 years) completed the Morningness-Eveningness Questionnaire (MEQ). Spatiotemporal gait parameters were recorded with three-dimensional motion capture during single-task walking and three dual-task conditions: backward word spelling (5LWB; phonological), serial subtraction by seven (SS7; arithmetic), and reverse month recitation (RMR; sequential). DTC was calculated for eight gait parameters. Condition differences were assessed with nonparametric tests and post-hoc comparisons. Multiple linear regression, adjusting for age, sex, BMI, and baseline gait velocity, tested the independent association between MEQ score and mean velocity DTC; exploratory Spearman correlations examined other parameters. SS7 produced the largest mean velocity DTC (-12.76%), significantly greater than 5LWB (-7.95%; p = 0.002) and RMR (-9.57%; p = 0.021). MEQ score independently predicted mean velocity DTC in 5LWB ({beta} = -0.51, p < 0.001, R{superscript 2} = 0.269) and RMR ({beta} = -0.55, p = 0.004, R{superscript 2} = 0.222), indicating greater morningness associated with better gait-speed preservation under cognitive load; the SS7 association was not significant ({beta} = -0.33, p = 0.071). Exploratory correlations showed MEQ-DTC associations across 7/8 parameters in 5LWB, 4/8 in RMR, and 3/8 in SS7. Chronotype is independently associated with dual-task gait cost in a task-domain-specific manner, with stronger effects for phonological and sequential tasks than for arithmetic processing. The SS7 condition yielded the largest interference but weakest chronotype modulation, suggesting arithmetic dual-task disruption may be less sensitive to circadian arousal. Fixed testing time and cross-sectional design warrant within-subject, multi-timepoint studies to confirm chronotype effects separate from time-of-day confounds.

BackgroundPaediatric liquid medicines (PLMs) routinely contain sucrose to improve palatability, yet their cariogenic potential is well established. Healthcare professionals awareness and prescribing practices regarding sugar-free PLMs have received limited study in India, particularly in Uttarakhand. MethodsA descriptive cross-sectional study was conducted among 500 healthcare professionals aged [&ge;]25 years, using a pilot-tested structured questionnaire (Cronbachs = 0.85), administered online and in person across Uttarakhand districts (January-March 2024). After excluding 69 incomplete responses, 431 participants were analysed (response rate: 86.2%), comprising general medicine practitioners (49%, n = 211), paediatricians (27%, n = 116), and dental practitioners (24%, n = 104). Descriptive statistics and chi-square tests were applied (p < 0.05). ResultsPrescription decisions were primarily driven by childs age and weight (58%), cost (40%), and pharmaceutical brand (37%). While 88% recognised PLM sweetness and 67% were aware of pH-dental harm links, only 20% associated PLMs with dental caries. Overall awareness of hidden sugars was 73%. Eighty-three percent knew of sugar-free alternatives (50% local availability), yet 80% found them less palatable and 85% costlier. Only 48% routinely provided oral health advice. A statistically significant association was found between specialty and sugar-free PLM awareness (p = 0.03), with dental practitioners recording the highest awareness (90%). ConclusionsHealthcare professionals demonstrated variable levels of knowledge, attitudes, and practices regarding PLMs, with critical gaps in caries recognition (20%) and oral health counselling (48%). Despite high sugar-free PLM awareness, uptake is constrained by perceived cost and palatability barriers. Targeted continuing medical education and policy measures, including sucrose-free labelling promotion, are needed to improve paediatric oral health outcomes in Uttarakhand. KEY MESSAGESO_LIOnly 20% of healthcare professionals in Uttarakhand associated pediatric liquid medicines (PLMs) with dental caries, representing a critical knowledge gap despite 88% recognising their sweetness. C_LIO_LIOverall awareness of hidden sugars in PLMs was 73%, yet only 48% routinely provided post-prescription oral health counsellingsubstantially below international benchmarks. C_LIO_LIEighty-three percent were aware of sugar-free PLM alternatives, but adoption was constrained by perceived inferior palatability (80%) and higher cost ([~]10% premium, cited by 85%). C_LIO_LIDental practitioners demonstrated significantly higher sugar-free PLM awareness than general practitioners and pediatricians (p = 0.03), supporting the case for interprofessional oral health education in medical training. C_LIO_LITargeted continuing medical education (CME) and policy measuresincluding sucrose-free labelling mandates and institutional formulary inclusionare needed to convert awareness into prescribing practice change. C_LI

Background: Sleep wake and circadian disturbances are increasingly recognised in people living with amyotrophic lateral sclerosis (plwALS), but endogenous circadian phase timing and its prognostic significance in early disease remain unclear. We assessed whether salivary dim-light melatonin onset (DLMO), an objective marker of central circadian phase, is altered in early plwALS and whether it provides prognostic information. Methods: In this prospective longitudinal observational study, plwALS within 18 months of symptom onset underwent home-based salivary melatonin sampling under dim light conditions at six predefined time points around habitual sleep onset (HSO). Melatonin profiles were modeled using cubic smoothing splines, and DLMO was defined as the first time the fitted curve reached 3 pg/mL. Clinical, respiratory, and sleep assessments were collected at baseline (T0) and after 6 months (T6); a subgroup repeated saliva sampling at T6. Age and sex matched controls underwent melatonin profiling. Associations with disease progression, incident respiratory symptoms, and survival/tracheostomy were examined using regressions and survival analyses. Results: Fifty plwALS were enrolled. Compared with controls, plwALS showed an earlier DLMO (20:24 vs 20:58; p=0.028) despite similar HSO and chronotype. Within ALS cohort, a later baseline DLMO correlated with worse functional/motor status, faster progression of disease, incident dyspnea/orthopnea by T6 (adjusted OR 3.02; p=0.017), and poorer survival/tracheostomy-free outcome. In re-sampled subgroup (n=28), DLMO and other melatonin-derived metrics did not change over 6 months. Conclusions: Circadian phase alterations are detectable in early ALS. Baseline DLMO may represent a non-invasive prognostic biomarker for progression, respiratory symptom emergence and survival, warranting validation in larger multicentre cohorts.

Patients with amyotrophic lateral sclerosis (ALS) face critical decisions regarding life-sustaining treatments, such as invasive mechanical ventilation and percutaneous endoscopic gastrostomy. Advance care planning and shared decision-making are standard supportive frameworks but they often fail to account for structural pressures like progressive decline, shifting patient values, and fear of becoming a burden that may influence decision-making. This study explores how patients with ALS interpret ventilator and care options amid progressive physical decline, thereby reconsidering approaches to decision support. Using a qualitative descriptive design, the researcher (a nurse/sociologist) conducted 2-3 hour home interviews with five purposively sampled patients with ALS. Data, including eye-tracking-aided responses, were analysed via Sandelowskis framework. Rigour was ensured through team-based triangulation, independent coding by two researchers, and a reflexive audit trail. Subjective narratives were prioritised without medical record cross-referencing to capture patients experiences. Four categories emerged: (1) Rewriting clinical prognosis into a narrative of exploration via peer models, where meeting active ventilator users transformed future perceptions; (2) The conflict between securing care infrastructure and the burden on family, which greatly influenced the will to survive; (3) Existential fluctuation, where patients intentions shifted with daily fulfilment and family events; and (4) Governance of the body via pre-emptive technology use and training carers as physical extensions. Findings showed decision-making was a multi-layered process redefining lifes meaning within social resources. This necessitate shifting from independent to relational autonomy, where agency relies on care infrastructure, not physical ability. Treatment choice is a dynamic exploration requiring narrative companions to support existential fluctuations. Professionals must coordinate environments to reduce patient indebtedness. Limitations include the small, resource-advantaged sample (N = 5) and reliance on subjective narratives without medical record verification. Living with ALS means governing a new self through relational support and continuous dialogue.

Background: Rett Syndrome (RTT) is a severe neurodevelopmental disorder affecting approximately 1 in 10,000 live female births worldwide. The Rett Syndrome Behaviour Questionnaire (RSBQ), remains one of the most widely used standardized behavioral assessment tools for RTT. However, the RSBQ was originally validated only in British English, limiting its applicability for Spanish-speaking caregivers and clinical centers across Latin America and Spain. Objective: The primary aim of this study was to develop and validate the comprehension of the Spanish translation of the RSBQ to ensure cultural and linguistic equivalence, enhance data reliability, and facilitate earlier, more accurate clinical assessments among Spanish-speaking RTT populations. Methods: Surveys were administered in two phases to Spanish-speaking caregivers between November 2023 and September 2025. Phase I consisted of 12 guided survey administrations with participants being able to ask clarifying questions and offer linguistic modifications of RSBQ questions. Phase II consisted of independent online administration of the refined Spanish RSBQ and a retest at least 7 days later. Participants were recruited through direct outreach and supported virtually during questionnaire completion. Results: Following data cleaning and quality control, a total of 51 caregivers successfully completed both surveys. The Spanish RSBQ demonstrated high caregiver comprehension and strong engagement across multiple Latin American countries, including Argentina, Mexico, and Peru. Responses were highly correlated between test and retest timepoints, and no question showed biased response distributions. A slight effect of response interval on test-retest correlation was observed, potentially indicating the impact of natural disease progression confounding retest evaluation for long (>80 day) intervals; however this effect did not impact the overall linguistic validation results as analysis of only <21 day test-retest responders confirmed the findings. Conclusions: This linguistic validation study represents the first formal step toward the clinical validation of the Spanish RSBQ, enabling broader inclusion of Spanish-speaking populations in RTT research. The collaborative, bilingual data collection strategy proved both feasible and effective, paving the way for multinational trials and expanding therapeutic accessibility through localized, patient-centered innovation.

ObjectiveTo describe the design, feasibility, and baseline characteristics of the Migraine Impact on Neurocognitive Dynamics (MIND) study, a 30-day smartphone-based cohort for high-frequency assessment of cognition and symptoms in adults with migraine. BackgroundCognitive symptoms are an important component of migraine burden, but they are difficult to measure using single-visit testing or retrospective questionnaires. Repeated smartphone-based assessment may better capture real-world variability in cognition and symptoms. MethodsAdults meeting International Classification of Headache Disorders, 3rd edition, criteria for migraine were enrolled remotely and completed 30 days of once-daily ecological momentary assessments and mobile cognitive tasks delivered through the Mobile Monitoring of Cognitive Change platform. Baseline measures assessed demographics, migraine characteristics, disability, mood, stress, and treatment patterns. Feasibility was evaluated using enrollment, completion, and retention metrics. ResultsA total of 177 participants enrolled (mean age 38.8 {+/-} 11.9 years; 79.7% female), including 80/177 (45.2%) with chronic migraine. Across the 30-day protocol, 3688 daily assessments were completed, representing 70.8% of all possible study days, and 70.6% of participants completed at least 20 days of monitoring. Completion remained above 60% across study days. At baseline, chronic migraine was associated with greater burden than low-frequency and high-frequency episodic migraine, including higher MIDAS scores (98.6 vs. 38.7 and 70.3), more days with concentration difficulty (16.0 vs. 7.9 and 11.5), and more days with functional interference (18.5 vs. 7.6 and 13.0). ConclusionsThe MIND study demonstrates the feasibility of high-frequency smartphone-based assessment of cognition and symptoms in migraine and provides a methodological foundation for future analyses of within-person cognitive and symptom dynamics across the migraine cycle.

Background: The etiology and nosological status of seasonal affective disorder (SAD) as a specifier of depressive episodes versus a transdiagnostic disorder are the subject of debate. In this study, we investigated the underlying etiology of SAD and dimensional seasonality by examining their association with latitude and genetic risk for a range of traits, and investigated gene-environment interactions. Methods: This study included 12,460 adults aged 18-90 with a history of depression from the Australian Genetics of Depression Study. Regression models included predictors for latitude (distance from equator) and polygenic scores for eight traits; major depressive disorder, bipolar disorder, anxiety disorders, chronotype, sleep duration, body mass index, vitamin D levels, and educational attainment. Outcomes were SAD status and general seasonality score. Results: SAD was positively associated with latitude (OR[95%CI] = 1.05[1.03-1.06], padjusted<0.001), and there was nominal evidence of additive and multiplicative interactions between chronotype genetic risk and latitude (OR = 0.99[0.99-0.99], padjusted=0.381; OR=0.98[0.97-0.99], padjusted=0.489). General seasonality score was associated with latitude (IRR=1.01[1.01-1.01], padjusted 0.001) and genetic risk for major depressive disorder (IRR =1.02[1.01-1.03], padjusted<0.001), bipolar disorder (IRR=1.02[1.01-1.03], padjusted=0.001), anxiety disorders (IRR=1.03[1.01-1.04], padjusted<0.001), vitamin D levels (OR=0.89[0.80-0.95], padjusted=0.048), and educational attainment (IRR=0.97[0.96-0.99], padjusted<0.001). Conclusions: These findings enhance understanding of SAD etiology, highlighting contributions of psychiatric genetic risk and geographic measures on seasonal behavior, and support examining seasonality as a continuous dimension.

Background: The instability-plasticity framework proposes that multimorbidity trajectories periodically enter instability phases that are vulnerable to escalation but also potentially modifiable through relational intervention. Whether such phases commonly resolve without acute care, or predominantly progress to hospitalisation, has not been quantified at scale. Objective: To quantify instability window outcomes across a longitudinal monitoring cohort; to test whether the characteristics distinguishing admitted from resolved windows reflect within-patient trajectory dynamics or between-patient severity; and to characterise which patient-reported and operator-rated signals reliably precede admission, using both a curated pilot sub-cohort and the full monitoring cohort with an explicit cross-cohort comparison. Methods: Two complementary analyses were conducted on data from the MonashWatch Patient Journey Record (PaJR) relational telehealth system. Instability windows were identified algorithmically (>=2 consecutive calls with Total_Alerts >=3) across the full longitudinal dataset (16,383 calls, 244 patients, 2.5 years) and classified by linkage to ED and hospital admission data. Window characteristics were compared at window, patient, and paired within-patient levels. Pre-admission signal cascades were analysed in two configurations: a curated pilot sub-cohort (64 patients, 280 calls, +/-10-day window, 103 admissions, December 2016-September 2017) and the full monitoring cohort (175 patients, 1,180 pre-admission calls, +/-14-day window, December 2016-July 2019). A three-way cross-cohort comparison decomposed differences between the two configurations into pipeline and population effects. Results: 621 instability windows were identified across 157 patients (64% of the monitored cohort). 67.3% resolved without hospital admission or ED attendance, a rate stable across alert thresholds 1-5. In paired within-patient analysis (n = 70), duration in days (p = 0.002) and multi-domain breadth (p < 0.001) distinguished admitted from resolved windows; alert intensity did not. In the pilot sub-cohort, patient-reported illness prognosis (Q21) was the dominant pre-admission signal (GEE beta = +0.058, AUC = 0.647, p-BH = 0.018). This finding did not replicate in the full cohort: Q21 was non-significant (GEE beta = -0.008, p = 0.154, AUC = 0.507). Cross-cohort analysis identified selective curation of the pilot sub-cohort as the primary explanation. In the full cohort, six signals escalated significantly before admission after Benjamini-Hochberg correction: total alerts, health impairment (Q26), red alerts, self-rated health (Q3), patient concerns (Q1), and operator concern (Q34). Health impairment achieved the highest individual AUC (0.605) and showed the longest pre-admission lead. No individual signal exceeded AUC 0.61. Conclusions: Two thirds of instability phases resolve without hospitalisation, providing direct empirical support for trajectory plasticity as a clinically frequent phenomenon. Within the same patient, persistence - in duration and in the consistency of high-severity multi-domain flagging across calls - distinguishes trajectories that tip into admission from those that resolve. The Q21 signal reversal between cohorts illustrates how selective curation can produce compelling but non-replicable findings in monitoring research. In the full population, objective alert signals and operator judgement, rather than patient illness prognosis, carry the pre-admission signal

Ancient DNA (aDNA) research has advanced rapidly with the development of high-throughput sequencing, which now enables genome-wide analyses of large collections of prehistoric specimens. However, analysing palaeontological and archaeological material with highly degraded DNA constitutes a major bioinformatic challenge. DNA from such samples is characterised by short fragment lengths, low endogenous content, post-mortem damage, and considerable cross-species contamination, which can increase spurious mapping and reference bias, affecting downstream population genetic inferences. Here we present DNAharvester, a modular and reproducible pipeline designed specifically for the processing of highly degraded DNA from ancient and historical specimens. DNAharvester integrates metagenomic filtering before mapping, competitive mapping, adaptive aligner selection (incorporating algorithms such as BWA-aln, BWA-mem, and Bowtie2), and systematic evaluation of reference bias and spurious mapping. By incorporating flexible mapping and filtering strategies, the pipeline can be adapted to varying sample preservation, with a distinct focus on maximising authentic data recovery from highly degraded material. Furthermore, DNAharvester features comprehensive subworkflows for iterative assembly of mitogenomes, identification of genomic repeats and CpG sites, taxonomic classification, microbial/pathogen screening of unmapped reads, genetic sex determination, and variant calling for downstream analyses. To accommodate datasets with varying sequencing depths, the pipeline incorporates multiple variant calling strategies, including diploid variant calling, genotype likelihood estimation, and pseudo-haploid random allele calling. Implemented in Nextflow, DNAharvester provides a highly scalable, containerised framework that enhances reproducibility, portability, and robustness in aDNA analyses. We validated the pipeline across a gradient of simulated scenarios and empirical datasets, demonstrating its ability to systematically mitigate complex background contamination while preserving authentic genomic signals even in the most challenging of circumstances. By streamlining complex bioinformatic tasks through simple configuration files, DNAharvester establishes a standardised approach for the rigorous analysis of highly degraded DNA datasets and makes genomic analyses of ancient remains accessible to the broader research community.